crossing96/oncoscreening huggingface dataset:
The evolution of PET imaging in renal, bladder, upper urinary tract urothelial, testicular and penile carcinoma - Today's impact, tomorrow's potential.	INTRODUCTION: The advancement of hybrid PET/CT or PET/MRI imaging for non-prostate genitourinary cancers has not experienced the rapid progress of prostate cancer. Nevertheless, these neoplasms are aggressive and reliable imaging plays a pivotal role in enhancing patients' quality of life and prognosis. AREAS COVERED: the main evidence regarding [(18)F]FDG and non-[(18)F]FDG PET/CT or PET/MRI in non-prostate uro-oncological malignancies are summarized and discussed. Moreover, potential future directions concerning PET imaging in these neoplasms are debated, with the aim to stimulate future research projects covering these fields. EXPERT OPINION: In Renal Cell Carcinoma (RCC), [(18)F]FDG PET/CT demonstrates varying efficacy in staging, restaging, and prognostic stratification, but PSMA PET/CT is emerging as a potential game-changer, particularly in advanced, high-grade aggressive clear cell RCC. [(18)F]FDG PET/CT may see an increased use in N and M-staging of bladder cancer, as well as for detecting recurrence and response to neoadjuvant chemotherapy. Preliminary data regarding [(68)Ga]-FAPI also looks promising in this context. [(18)F]FDG PET/MRI could be useful for the T-staging of bladder cancer, while upper tract urothelial carcinoma still lacks of molecular imaging literature reports. In testicular and penile cancer [(18)F]FDG PET/CT has demonstrated its usefulness in several clinical settings, although experiences with non-[(18)F]FDG radiotracers are lacking.	bladder
Identification and validation of telomerase related lncRNAs signature to predict prognosis and tumor immunotherapy response in bladder cancer.	Telomerase allows eukaryotic cells to proliferate indefinitely, an important characteristic of tumor cells. Telomerase-related long no coding RNAs (TERLs) are involved in prognosis and drug sensitivity prediction; however, their association with bladder cancer (BLCA) is still unreported. The objective of this research is to determine a predictive prognostic TERL signature for OS and to provide an efficient treatment option for BLCA. The RNA sequence, clinical information, and mutational data of BLCA patients were acquired from The Cancer Genome Atlas (TCGA) database. With the help of the data from least absolute shrinkage and selection operator (LASSO) regression and Cox regression, a prognostic signature was established including 14 TERLs, which could divide BLCA patients into low-risk (L-R) and high-risk (H-R) cohorts. The time-dependent receiver operating characteristic (ROC) curve demonstrated the greater predictive power of the model. By combing the TERLs-based signature and clinical risk factors (age, sex, grade, and stage), a prognostic nomogram was constructed to forecast the survival rates of patients with BLCA at 1-, 3-, and 5-years, which was well matched by calibration plots C-index and Decision curve analysis (DCA). Furthermore, the L-R cohort showed higher tumor mutation burden (TMB) and lower tumor immune dysfunction and exclusion (TIDE) than the H-R cohort, as well as substantial variability in immune cell infiltration and immune function between the two cohorts was elucidated. As for external validation, LINC01711 and RAP2C-AS1 were identified as poor prognostic factors by survival analysis from the Kaplan-Meier Plotter database, which were validated in BLCA cell lines (EJ, 253J, T24, and 5637) and SV-HUC-1 cells as the control group using qRT-PCR. In addition, interference with the expression of RAP2C-AS1 suppresses the proliferation and migration of BLCA cells, and RAP2C-AS1 could affect the expression of CD274 and CTLA4, which could serve as prognostic markers and characterize the tumor microenvironment in BLCA. Overall, the model based on the 14-TERLs signature can efficiently predict the prognosis and drug treatment response in individuals with bladder cancer.	bladder
MicroRNA-152 specifically targets kinesin family member 14 to suppress the advancement of bladder cancer cells via PI3K/AKT pathway.	BACKGROUND: Kinesin family member 14 (KIF14) overexpression has been linked to tumor progression and metastasis in different malignancies, but its precise molecular mechanism in bladder cancer (BLCA) remains unclear. METHODS: The expression of KIF14 in BLCA and its relationship with clinical outcomes were assessed. Functional investigations on KIF14 were conducted using CCK-8, Transwell experiment, colony formation, scratch motility assays, and flow cytometry. We examined the downstream route of KIF14 and identified its upstream regulatory factor through luciferase reporter experiments and bioinformatics tools. RESULTS: Our findings demonstrated that increased KIF14 expression was associated with poor survival prognosis in BLCA patients. Deletion of KIF14 affected cell cycle progression, induced apoptosis, and inhibited cell growth, migration, and invasion. GSEA analysis revealed a strong association between KIF14 expression and the PI3K/AKT signaling pathway. Further research showed that KIF14 deletion decreased the levels of p-PI3K, p-AKT, FOXM1, and CCNB1. We also found that has-miR-152-3p (miR-152) suppressed BLCA cell growth by post-transcriptionally regulating KIF14 expression. CONCLUSIONS: Our findings suggest that targeting KIF14 could alter the PI3K/AKT and FOXM1-CCNB1 axis, leading to growth inhibition, cell cycle arrest, and induction of apoptosis in BLCA cells. Additionally, miR-152 directly regulates KIF14 expression at the post-transcriptional level. Overall, KIF14 represents a promising therapeutic target for BLCA clinical therapy.	bladder
ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape.	Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.	bladder
Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.	OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.	bladder
TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor-Naïve Locally Advanced or Metastatic Urothelial Carcinoma.	We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/μL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/μL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC. Clinical Trial Registration: JapicCTI-183824.	bladder
Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies.	Bladder tumors have a high mutational burden and tend to be responsive to immune therapies; however, response rates remain modest. To date, immunotherapy in bladder cancer has largely focused on enhancing T-cell immune responses in the bladder tumor microenvironment. It is anticipated that other immune cells, including innate lymphoid cells (ILC), which play an important role in bladder oncogenesis and tumor suppression, could be targeted to improve response to existing therapies. ILCs are classified into five groups: natural killer cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. ILCs are pleiotropic and play dual and sometimes paradoxical roles in cancer development and progression. Here, a comprehensive discussion of the current knowledge and recent advancements in understanding the role of ILCs in bladder cancer is provided. We discuss the multifaceted roles that ILCs play in bladder immune surveillance, tumor protection, and immunopathology of bladder cancer. This review provides a rationale for targeting ILCs in bladder cancer, which is relevant for other solid tumors.	bladder
Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?	BACKGROUND: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching. STUDY DESIGN AND METHODS: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer-specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio. RESULTS: We screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p < .001). Postoperative transfusions were associated with better OS (p = .004) and CSS (p = .008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis. DISCUSSION: In our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis. However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits.	bladder
Near Complete Response to Platinum-based Systemic Chemotherapy in High-risk Upper Tract Urothelial Carcinoma With an ERBB2 Gene Mutation: A Case Report.	In bladder urothelial carcinoma, ERBB2 mutations have been associated with favorable response to platinum-based neoadjuvant chemotherapy. However, this association has not been reported in upper tract urothelial carcinoma (UTUC). We describe an excellent response to cisplatin-based chemotherapy in metastatic UTUC with an ERBB2 mutation. Our patient is a 54-year-old female with metastatic UTUC who received systemic cisplatin and gemcitabine. Postchemotherapy imaging demonstrated decreased size of pyelocaliceal mass and decreased retroperitoneal adenopathy compared to initial imaging. Surgical pathology from consolidative resection showed 3 mm residual renal tumor and no viable lymph node disease. Genomic testing demonstrated an ERBB2 gain of function mutation.	bladder
Effect and Mechanism of Curdione Combined with Gemcitabine on Migration and Invasion of Bladder Cancer.	Bladder cancer (BCa), which usually occurs in bladder epithelial cells and is the fifth most common type of cancer in the world. he recurrence rate within 5 years after surgery is 0.8-45% of patients with early bladder cancer. Therefore, finding appropriate drug therapy for patients with bladder cancer can provide a reference for clinical treatment and play an important role in improving the prognosis of patients. In this study, CCK8 assay result showed that the inhibition of bladder cancer cell activity by Curdione and GEM increased with time and dose. Subsequently, CCK8, clone formation assay and Transwell result showed Curdione enhances GEM inhibition of bladder cancer cell activity, clonal formation and migration, these combine therapeutic schedule also could inhibited growth of in vivo xenograft tumors. The comprehensive database showed that CA2 is a potential target genes of Curdione, and Knockdown CA2 enhances GEM induced inhibition of cell proliferation and migration. Based on these advantages, Curdione may be a new type of action drug or adjunct for the treatment of bladder cancer.	bladder
Evaluation of the safety and feasibility of electrochemotherapy with intravenous bleomycin as local treatment of bladder cancer in dogs.	Local treatment of canine urothelial carcinoma (UC) of the bladder is a challenge. More than 90% of the cases invade the muscular layer, more than 50% develop on bladder sites with a difficult surgical approach and often requiring radical surgical procedures. This study aims to evaluate the safety and feasibility of electrochemotherapy (ECT) with intravenous bleomycin (BLM) as a local therapy for bladder UC. This prospective study included 21 dogs with spontaneous bladder UC. Regional/distant metastases and neoplastic infiltration of the serosa was considered the main exclusion criteria. We had no deaths during ECT or in the immediate postoperative period, and no suture dehiscence. Most dogs (19/21) developed mild adverse effects, whereas two dogs developed ureteral stenosis. Complete response (CR) was achieved in 62% of the cases (13/21), while partial response (PR) was achieved in 24% (5/21). The median survival and disease-free survival times were 284 and 270 days, respectively. Overall survival was significantly better in the dogs who achieved a CR. In conclusion, ECT was well-tolerated in dogs with UC, demonstrating its safety and feasibility. These data pave the way for new studies aimed at evaluating the effectiveness of ECT in canine bladder UC as a translational model for human disease.	bladder
The bladder microbiota is not significantly altered by intravesical BCG therapy.	INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.	bladder
Organ-specific Tumor Response to Avelumab Maintenance Therapy for Advanced Urothelial Carcinoma: A Multicenter Retrospective Study.	BACKGROUND/AIM: The organ-specific therapeutic effects of avelumab for the maintenance treatment of advanced urothelial carcinoma (UC) are unclear. PATIENTS AND METHODS: Patients who received avelumab for advanced UC that had not progressed with first-line platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The organ-specific response was evaluated, and progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: We analyzed 42 patients (male, n=31; median age, 72 years). The overall response rate [complete response (CR)+ partial response (PR)] and disease control rate (CR+PR+stable disease) were 2.4% and 47.6%, respectively. In total, 27, 11, 8 and 5 patients had measurable lymph node [organ-specific response rate (OSRR) 7.4%, organ-specific disease control rate (OSDCR) 59.3%], lung (OSRR 18.2%, OSDCR 36.4%), primary tumor organ (OSRR 0%, OSDCR 100%) and liver (OSRR 0%, OSDCR 100%) disease, respectively. The median PFS and OS was 3.8 months and 20.2 months, respectively. Regarding organ-specific PFS, a log-rank test confirmed significant differences between patients with and without primary tumor organ disease (p=0.009) and patients with and without liver metastasis (p=0.015). Regarding organ-specific OS, a log-rank test revealed no significant differences between patients with and without metastatic disease for all organs (lung: p=0.835; lymph node: p=0.914; bone: p=0.257; primary tumor: p=0.057; liver: p=0.893). CONCLUSION: In patients receiving avelumab maintenance therapy, no significant differences in OS were observed between patients with and without metastasis to any organ, including the primary organ, although metastases and the primary tumor organ disease showed different responses.	bladder
CD271 promotes proliferation and migration in bladder cancer.	Bladder cancer is a urothelial cancer and effective therapeutic strategies for its advanced stages are limited. Here, we report that CD271, a neurotrophin receptor, promotes the proliferation and migration of bladder cancer cells. CD271 knockdown decreased proliferation in both adherent and spheroid cultures, and vice versa when CD271 was overexpressed in bladder cancer cell lines. CD271 depletion impaired tumorigenicity in vivo. Migration activity was reduced by CD271 knockdown and TAT-Pep5, a known CD271-Rho GDI-binding inhibitor. Apoptosis was induced by CD271 knockdown. Comprehensive gene expression analysis revealed alterations in E2F- and Myc-related pathways upon CD271 expression. In clinical cases, patients with high CD271 expression showed significantly shortened overall survival. In surgically resected specimens, pERK, a known player in proliferation signaling, colocalizes with CD271. These data indicate that CD271 is involved in bladder cancer malignancy by promoting cell proliferation and migration, resulting in poor prognosis.	bladder
Reparameterized multiobjective control of BCG immunotherapy.	Bladder cancer is a cancerous disease that mainly affects elder men and women. The immunotherapy that uses Bacillus of Calmette and Guerin (BCG) effectively treats bladder cancer by stimulating the immune response of patients. The therapeutic performance of BCG relies on drug dosing, and the design of an optimal BCG regimen is an open question. In this study, we propose the reparameterized multiobjective control (RMC) approach for seeking an optimal drug dosing regimen and apply it to the design of BCG treatment. This approach utilizes constrained optimization based on a nonlinear bladder cancer model with impulsive drug instillation. We compare the performance of RMC with Koopman model predictive control (MPC) and validate the efficacy of optimal BCG dosing regimens through numerical simulations, demonstrating the efficient elimination of cancerous cells. The proposed control framework holds the potential for generalization to other model-based treatment designs.	bladder